174174-99-3Relevant academic research and scientific papers
Synthesis of 5'-fluoro-5'-deoxy- and 5'-amino-5'-deoxytoyocamycin and sangivamycin and some related derivatives
Sharma,Li,Ledvina,Bobek
, p. 1831 - 1852 (2007/10/02)
A series of 5'-substituted analogs of toyocamycin were prepared by condensation of silylated 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine with protected 5-azido-5-deoxy- or 5-fluoro-5-deoxyribofuranose followed by debromination and deblocking. Alternatively, 5'-azido-5'-deoxytoyocamycin was prepared by azidation of toyocamycin. Conversion of the 5-nitrile function of the toyocamycin derivatives into a carboxamide or a thiocarboxamide gave the corresponding analogs of sangivamycin or thiosangivamycin while reduction of the 5'-azido-5'-deoxy nucleosides provided 5'-amino-5'-deoxy derivatives.
New Adenosine Kinase Inhibitors with Oral Antiinflammatory Activity: Synthesis and Biological Evaluation
Cottam, Howard B.,Wasson, D. Bruce,Shih, Hsien C.,Raychaudhuri, Anil,Pasquale, Gene Di,Carson, Dennis A.
, p. 3424 - 3430 (2007/10/02)
Several 5-iodotubercidin analogues in the pyrazolopyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials.The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor.First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity.The order of potency was: iodotubercidin > hydroxyl > amino deoxy > fluoro > chloro >> azido.The Ki values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively.The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out.Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds.The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective.Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally.Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts.Results indicated that the two most potent inhibitors in the pyrazolopyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.
